Variant 17-58193077-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000502.6(EPX):c.116G>A(p.Cys39Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,612,604 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 13 hom. )

Consequence

EPX
NM_000502.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.43

Variant links:

Genes affected

EPX (HGNC:3423): (eosinophil peroxidase) This gene is a member of the peroxidase gene family and is expressed in eosinophils. The encoded preproprotein is proteolytically processed into covalently attached heavy and light chains to form the mature enzyme, which functions as an oxidant. The enzyme is released at sites of parasitic infection or allergen stimulation to mediate lysis of protozoa or parasitic worms. The gene is found in a gene cluster with other peroxidase genes on chromosome 17. Mutations in this gene result in eosinophil peroxidase deficiency. [provided by RefSeq, Feb 2016]

EPX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073302686).

BP6

Variant 17-58193077-G-A is Benign according to our data. Variant chr17-58193077-G-A is described in ClinVar as [Benign]. Clinvar id is 782915.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00112 (169/151430) while in subpopulation EAS AF= 0.0216 (111/5136). AF 95% confidence interval is 0.0184. There are 4 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPX	NM_000502.6 linkuse as main transcript	c.116G>A	p.Cys39Tyr	missense_variant	2/13	ENST00000225371.6	NP_000493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6 linkuse as main transcript	c.116G>A	p.Cys39Tyr	missense_variant	2/13	2	NM_000502.6	ENSP00000225371	P1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

151312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0218

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00386

GnomAD3 exomes

AF:

0.00169

AC:

425

AN:

251480

Hom.:

AF XY:

0.00159

AC XY:

216

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0212

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000449

AC:

656

AN:

1461174

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

294

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0105

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.00112

AC:

169

AN:

151430

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74000

show subpopulations

Gnomad4 AFR

AF:

0.00112

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0216

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00382

Alfa

AF:

0.000952

Hom.:

Bravo

AF:

0.00119

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00157

AC:

191

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0073

MetaSVM

Uncertain

0.028

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.81

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.98

Vest4

0.26

MVP

0.85

MPC

0.22

ClinPred

0.076

GERP RS

4.2

Varity_R

0.36

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over